Drug interactions occur when a drug's mechanism of action is affected by the concomitant administration of substances such as foods, beverages, or other drugs. The cause is often inhibition of, or less effective action, of the specific receptors available to the drug. This influences drug molecules to bind to secondary targets, which may result in an array of unwanted side-effects. The term selectivity describes a drug’s ability to target a single receptor, rendering a predictable physiological response. For example, the binding of acetylcholine to muscarinic tracheal smooth-muscle receptors (M3) results in smooth muscle contractions.
When freely binding receptors interact with agonist- chemicals that activate receptors - and antagonists- that inhibit/ block activation - the opportunity for selective drugs to bind with the intended receptor cells decreases as most receptors are already accounted for. Therefore, the drugs are more likely to bind to other receptors relative to the intended receptor, causing different effects. For example, consuming both Zolpidem (i.e., Ambien) and alcohol together, both which affect the GABAA receptors, results in the overstimulation of this receptor, which can lead to loss of consciousness. The risk of a drug-drug interaction (DDI) increases with the number of drugs used. Over a third (36%) of the elderly in the U.S. regularly use five or more medications or supplements, and 15% are at risk of a significant drug-drug interaction.
Based on pharmacodynamics
Drug interactions can be additive (the result is what you expect when you add together the effect of each drug taken independently), synergistic (combining the drugs leads to a larger effect than expected), or antagonistic (combining the drugs leads to a smaller effect than expected). On some occasions, it is difficult to distinguish between synergistic or additive interactions, since the individual effects of each drug may vary from patient to patient. A synergistic interaction may be beneficial for patients, but may also increase the risk of overdose. Drug interaction predictors enable risk assessment of multiple drugs simultaneously with visualizations of risk per therapeutic class, to indicate a spectrum from no risk to high risk.
Both synergy and antagonism can occur during different phases of the interaction between a drug and an organism. The different responses of a drug receptor have resulted in several classifications, such as partial agonist, competitive agonist, an inverse agonist. These concepts have fundamental applications in the pharmacodynamics of these interactions. The proliferation of existing classifications at this level and lack of knowledge around drug mechanisms means that it is difficult to offer a clear classification for these concepts. It is possible that authors would misapply any given classification.
Direct interactions between drugs are also possible and may occur when two drugs are mixed before intravenous injection. For example, mixing thiopentone and suxamethonium can lead to the precipitation of thiopentone.
The change in an organism's response upon administration of a drug is an important factor in pharmacodynamic interactions. These changes are extraordinarily difficult to classify given the wide variety of modes of action that exist, and the fact that many drugs can cause their effect through several different mechanisms. This wide diversity also means that in all but the most obvious cases, it is important to investigate and understand these mechanisms. A well-founded suspicion exists that there are more unknown interactions than known ones.